5–aminolevulinic acid fluorescence-guided surgery vs conventional white-light resection in glioma: A systematic review and meta-analysis.

e14076 Background: Gliomas are the most common primary malignant brain tumors, for which maximal safe surgical resection is a cornerstone of management to improve survival outcomes. The infiltrative nature of these tumors, however, makes distinguishing neoplastic from healthy tissue challenging with conventional white-light microsurgery. Fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) has emerged as a tool to enhance intraoperative tumor visualization, but its long-term impact requires clarification. This systematic review and meta-analysis aims to evaluate the efficacy and safety of 5-ALA-guided resection compared to conventional surgery for newly diagnosed gliomas. Methods: A systematic literature search was conducted across multiple databases up to July 2025, including randomized controlled trials (RCTs) and cohort studies that compared 5-ALA FGS with standard white-light microsurgical resection in patients with newly diagnosed glioma. The primary outcomes were the rate of gross total resection (GTR), progression-free survival (PFS), and overall survival (OS). The incidence of new postoperative neurological deficits was assessed as a primary safety outcome. Data were pooled for meta-analysis using random-effects models. Results: Thirteen studies, comprising three RCTs and ten retrospective studies, were included in the final analysis, with a total of 2,211 patients. The meta-analysis revealed that the use of 5-ALA was associated with a significantly higher rate of GTR compared to the control group (Risk Ratio [RR] = 1.73, 95% Confidence Interval [CI] 1.57–1.91, p < 0.0001). This improvement in resection correlated with a significant benefit in 6-month PFS (RR = 1.46, 95% CI 1.08–1.99, p = 0.026) and 12-month OS (RR = 1.21, 95% CI 1.07–1.37, p = 0.0027). No significant difference was observed for 12-month PFS (p = 0.417) or the incidence of new neurological deficits between the two groups (RR = 1.29, 95% CI 0.62–2.69, p = 0.435). Conclusions: This meta-analysis provides strong evidence that 5-ALA fluorescence-guided surgery significantly increases the rate of gross total resection in patients with newly diagnosed glioma. This translates into improved short- and medium-term survival outcomes without an increased risk of postoperative neurological morbidity. These findings support the integration of 5-ALA as a standard of care in the surgical management of high-grade gliomas to maximize the extent of resection and improve patient outcomes.